Multimarker Strategy for Heart Failure Prognostication. Value of Neurohormonal Biomarkers: Neprilysin vs NT-proBNP.

Abstract

INTRODUCTION AND OBJECTIVES:

Neprilysin breaks down numerous vasoactive peptides. The soluble form of neprilysin, which was recently identified in heart failure, is associated with cardiovascular outcomes. Within a multibiomarker strategy, we directly compared soluble neprilysin and N-terminal pro-B-type natriuretic peptide as risk stratifiers in a real-life cohort of heart failure patients.

METHODS:

Soluble neprilysin, N-terminal pro-B-type natriuretic peptide, ST2, and high-sensitivity troponin T levels were measured in 797 consecutive ambulatory heart failure patients followed up for 4.7 years. Comprehensive multivariable analyses and soluble neprilysin vs N-terminal pro-B-type natriuretic peptide head-to-head assessments of performance were performed. A primary composite endpoint included cardiovascular death or heart failure hospitalization. A secondary endpoint explored cardiovascular death alone.

RESULTS:

Median soluble neprilysin and N-terminal pro-B-type natriuretic peptide concentrations were 0.64ng/mL and 1187 ng/L, respectively. Both biomarkers significantly correlated with age (P<.001) and ST2 (P<.001), but only N-terminal pro-B-type natriuretic peptide significantly correlated with estimated glomerular filtration rate (P<.001), body mass index (P<.001), left ventricular ejection fraction (P=.02) and high-sensitivity troponin T (P<.001). In multivariable Cox regression analyses, soluble neprilysin remained independently associated with the composite endpoint (hazard ratio=1.14; 95% confidence interval, 1.02-1.27; P=.03) and cardiovascular death (hazard ratio=1.15; 95% confidence interval, 1.01-1.31; P=.04), but N-terminal pro-B-type natriuretic peptide did not. The head-to-head soluble neprilysin vs N-terminal pro-B-type natriuretic peptide comparison showed good calibration and similar discrimination and reclassification for both neurohormonal biomarkers, but only soluble neprilysin improved overall goodness-of-fit.

CONCLUSIONS:

When added to a multimarker strategy, soluble neprilysin remained an independent prognosticator, while N-terminal pro-B-type natriuretic peptide lost significance as a risk stratifier in ambulatory patients with heart failure. Both biomarkers performed similarly in head-to-head analyses.

• Authors: Antoni Bayes-Genis, Jaume Barallat, Amparo Galán, Marta de Antonio, Mar Domingo, Elisabet Zamora, Paloma Gastelurrutia, Joan Vila, Judith Peñafiel, Carolina Gálvez-Montón, Josep Lupón
• Journal: Revista espanola de cardiologia (English ed.) (Rev Esp Cardiol (Engl Ed)) Vol. 68 Issue 12 Pg. 1075-84 (Dec 2015) ISSN: 1885-5857 [Electronic] Spain
• PMID: 26297179 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Chemical References

• Biomarkers
• Peptide Fragments
• Troponin T
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain
• Neprilysin

Topics

• Aged
• Biomarkers (metabolism)
• Cardiovascular Diseases (mortality)
• Epidemiologic Methods
• Female
• Heart Failure (diagnosis, mortality, physiopathology)
• Hospitalization (statistics & numerical data)
• Humans
• Male
• Natriuretic Peptide, Brain (metabolism)
• Neprilysin (metabolism)
• Peptide Fragments (metabolism)
• Prognosis
• Stroke Volume (physiology)
• Troponin T (metabolism)
• Ventricular Dysfunction, Left (mortality, physiopathology)